Interictal spikes in developing rats cause long-standing cognitive deficits.
Interictal spikes in developing rats cause long-standing cognitive deficits.
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DOI：
10.1016/j.nbd.2010.05.002
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发表时间：
2010-09
影响因子：
6.1
通讯作者：
Holmes, Gregory L.
中科院分区：
文献类型：
--
作者：
Khan, Omar I.;Zhao, Qian;Miller, Forrest;Holmes, Gregory L.
癫痫性脑病患儿的脑电图中常见发作间期棘波。虽然众所周知，发作间期棘波是癫痫发作的生物标志物，可导致短暂的认知障碍，但尚不清楚发作间期棘波是否会对儿童的学习和记忆产生长期不良影响。在这里，我们研究了未发生癫痫发作的幼鼠发作间期棘波对长期学习和记忆的影响。在连续的脑电图监测期间，对幼鼠连续10天给予4小时低剂量的氟乙酸。大鼠发作间期棘波没有癫痫发作，而年龄匹配的对照组在类似的测试条件下有几个发作间期棘波。当大鼠作为成年人进行测试时，在Morris水迷宫的探测测试中存在参考记忆损伤，在四次试验的径向臂水迷宫中存在参考记忆损伤，并且存在受损的长时程增强。早期生活发作间期尖峰导致受损的新细胞形成和海马细胞计数减少，但没有引起细胞凋亡的增加。这项研究首次证明，在没有癫痫发作的幼鼠中，发作间期棘波可导致长期的空间认知障碍。我们的研究结果表明，在大脑发育过程中，抑制IIS可能与治疗癫痫发作一样重要。
Frequent interictal spikes are a common finding in the electroencephalograms of children with epileptic encephalopathies. While it is well recognized that interictal spikes are a biological marker of seizures and can lead to transitory cognitive impairment, whether interictal spikes can result in long-standing adverse effects on learning and memory in children is not known. Here we investigated the consequences of interictal spikes in rat pups without seizures on long-term learning and memory. Rat pups were given a low dose of flurothyl for four hours for 10 days during continuous electroencephalographic monitoring. Rats developed interictal spikes without seizures while age-matched controls under similar testing conditions had few interictal spikes. When rats were tested as adults, there was impairment in reference memory in the probe test of the Morris water maze, reference memory impairment in the four-trial radial-arm water maze and impaired long-term potentiation. Early-life interictal spikes resulted in impaired new cell formation and decreased cell counts in the hippocampus but did not cause an increase in apoptosis. This study, for the first time demonstrates that interictal spikes in rat pups without seizures can result in long-standing spatial cognitive impairment. Our findings suggest that suppressing IIS may be as important as treating seizures during brain development.
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影响因子：
11.2
作者：
Holmes, GL;Gairsa, JL;Ben-Ari, Y
通讯作者：
Ben-Ari, Y
DOI：
10.1016/s0165-3806(99)00135-2
发表时间：
1999-12-10
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Huang, LT;Cilio, MR;Holmes, GL
通讯作者：
Holmes, GL
影响因子：
2.2
作者：
Karnam, Havisha B.;Zhao, Qjan;Holmes, Gregory L.
通讯作者：
Holmes, Gregory L.
影响因子：
11.2
作者：
Cornejo, Brandon J.;Mesches, Michael H.;Benke, Timothy A.
通讯作者：
Benke, Timothy A.
影响因子：
2.6
作者：
Besag, FMC
通讯作者：
Besag, FMC